Research Leads to Unexpected Discovery

May enhance efforts to control a common soybean pathogen

WOOSTER, Ohio — Sometimes the serendipity of science leads researchers into areas
they never imagined. In the case of College of Wooster Professors Dean Fraga (Danforth
Professor of Biology) and Mark Snider (Associate Professor of Chemistry), their efforts
to understand how proteins work and evolve new functions may have led them to the
center of an area of importance to Ohio farmers, including many in Wayne County.

Molecular biologists often wonder how different proteins evolved to do what they do.
The hope is that by understanding this process in detail they will be in a better
position to design new proteins that can help solve medical, environmental, or industrial
problems in the future. Fraga and Snider approach this larger question by studying
the molecular evolution of the Phosphagen Kinases (PK), a family of enzymes that play
a critical role in energy metabolism in the cell. That energy can give organisms an
extra burst when, for example, they are attempting to flee from predators, or in the
case of a pathogen, mount an infection by evading or disabling a host’s defenses.
In the course of their research, Fraga and his associates have discovered that this
enzyme may have evolved several unique properties much earlier in its evolutionary
history than previously thought.

“We now understand that protozoa had considerable diversity in the substrates they
could use and the structures the proteins could adopt,” says Fraga. “This has a big
impact on how we imagined this family evolved into the forms we see today, including
the version of the protein in our own bodies.”

While that may be interesting to the science community, it doesn’t mean much to the
general public, except for the fact that in their efforts to understand how the protein
evolved, this research team stumbled onto a substrate of a particular PK that could
help local farmers and society as a whole. What they learned was that a devastating
pathogen to many different crops, including soybeans, potatoes, and peppers, has a
version of the PK that is not seen in many species and may be a useful target for
a pesticide designed to control the pest. The pathogen they studied is Phytophthora sojae, which infects soybeans — one of Ohio’s most abundant and profitable crops. However,
what they have found is true for all Phytophthora species, including those that infect peppers and potatoes.

Their hope is that by blocking the function of this protein and thereby disrupting
the energy production of the pest, they could prevent it from destroying a farmer’s
field. They plan to work with other researchers to explore the feasibility of developing
a chemical that when sprayed on a field can penetrate the pathogen, bind to the PK
protein, and disable the process of energy homeostasis, thereby crippling the pathogen’s
ability to mount an infection and preventing it from damaging the cells.

“It speaks to the serendipity of science,” says Snider. “We were interested in the
evolution of phosphagen kinase, but in the process we discovered a possible application
that could have a very beneficial application in agriculture.”

This work was funded in part by a United States Department of Agriculture (USDA) grant
given to a team of researchers headed by Brett Tyler, Stewart Professor of Gene Research
at Oregon State University to better understand the Phytophthora family of pathogens. Fraga and Snider’s team included three recent Wooster graduates:
Allyson Palmer, Brittany Begres, and Jason Van Houton.

Fraga also noted that his long-term relationship with the nearby Ohio Agricultural
Research and Development Center (OARDC) played a vital role, specifically his acquaintance
with Dr. Anne Dorrance, who provided a P. sojae genomic sample from which the PK gene was cloned. In addition, the researchers at
the OARDC provided valuable advice as this project has developed.

“Our recent experience is a great example of how basic science can lead to unexpected
discoveries,” says Fraga, “and how those discoveries can lead to findings with important
applications in the real world. The best part, however, is that our students have
an opportunity to be partners in this discovery.”